HIV-specific cellular immunity is hampered in most HIV-infected individuals. Therapeutic immunization in HIV aims to strengthen the HIV-specific cellular immunity, usually in the absence of replicating HIV with antiretroviral drugs. The aims of this strategy can be to decrease the mass of latently infected CD4+ T cells, better tolerance of drug-free periods, and better select candidates for preventive HIV vaccines.

Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four, slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal injections using GM-CSF as adjuvant. A recent multinational placebo-controlled study found improvement of vaccine-specific T cell immunity and decrease in viral loads (presented at the AIDS vaccine 2011 conference, Bangkok).

In this study the investigators hypothesize that the Vacc-4x peptides, deposited on the nasal mucosal surfaces in conjunction with Endocine, a newly developed and documented mucosal adjuvant, will induce T cell responses to HIV and improve HIV-specific immunity both systemically and at mucosal surfaces (oral, rectal, vaginal).

Evaluate the safety of intranasal administration of Vacc-4x with Endocine as adjuvant at three different dose levels [ Time Frame: 2 months after completion of last patient. ] [ Designated as safety issue: Yes ]

Record adverse events including severe adverse events according to GCP

Secondary Outcome Measures:

Evaluate cellular immune response to Vacc-4x in vivo by Vacc-4x DTH skin test [ Time Frame: Up to 2 months after completion of last patient ] [ Designated as safety issue: No ]

80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity

Biological: Vacc-4x low dose

80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks

Other Names:

Vacc-4x

Endocine

Experimental: Vacc-4x medium dose

400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity

Biological: Vacc-4x medium dose

400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks

Other Names:

Vacc-4x

Endocine

Experimental: Vacc-4x high dose

1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity

Biological: Vacc-4x high dose

1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks

Other Names:

Vacc-4x

Endocine

Placebo Comparator: Zero dose

Adjuvant only, i.e. 300 µl Endocine divided into two administrations, one for each nose cavity

Biological: Zero dose

300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks

Other Name: Endocine

Detailed Description:

HIV-specific cellular immunity is hampered in most HIV-infected individuals, partly because the virus infects CD4+ T cells, the key cell subset in all immune responses. CD4 is the primary HIV receptor (CD4), but infection requires a co-receptor (CCR5) which is carried mainly by activated T cells. During primary HIV-infection, two types of CD4+ T cells mainly become infected: (i) Sub-activated T cells of all specificities within the mucosal linings, particularly in the gut; and (ii) HIV-specific T cell clones, that proliferates and are activated as a normal response to HIV infection itself. The HIV-specific immunity therefore becomes severely compromised early in the infection. Patients having better T cells specific to parts of the HIV Gag matrix protein usually progress slower towards AIDS than patients with poor T cell responsitivity towards Gag.

Therapeutic immunization in HIV aims to strengthen the HIV-specific cellular immunity, usually in the absence of replicating HIV with antiretroviral drugs. The aims of this strategy can be to decrease the mass of latently infected CD4+ T cells, better tolerance of drug-free periods, and better select candidates for preventive HIV vaccines. The latter point may be important since clinical trials with preventive vaccine candidates may challenge our ethical standards: Such trials must be very large and conducted in poor areas with high prevalence of HIV, in order to have as many (placebo) or few (vaccine candidate) new HIV infections as fast as possible. Preventive vaccine trials might therefore compete with introduction of "western" access to HIV drugs.

Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four, slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal injections using GM-CSF as adjuvant. In a dose study at our Hospital, the investigators found induction of robust cellular immune responses both in vitro and in vivo by skin testing, indications of improved viral control, long-lasting immunity and lack of mutational changes in the HIV strains within the study cohort. A recently completed multinational placebo-controlled study found improvement of viral loads (presented at the AIDS vaccine 2011 conference, Bangkok).

In this study the investigators hypothesize that the Vacc-4x peptides, deposited on the nasal mucosal surfaces in conjunction with Endocine, a newly developed and documented mucosal adjuvant, will induce T cell responses to HIV and improve HIV-specific immunity both systemically and at mucosal surfaces (oral, rectal, vaginal). This route of application may even simplify mass vaccination. The study is primarily a dose-study focused on adverse events, which have been negligible when Vacc-4x was given parenterally, as well as induction of systemic and mucosal immunity.

Eligibility

Ages Eligible for Study:

18 Years to 70 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Age above 18 years, both genders.

HIV positive at least one year.

Clinically stable on ART for the last 6 months (changes in therapy is allowed as long as the viral load is stable).

Documented viral load (HIV-1 RNA) less than 50 copies/mL for the last six months.

Women of childbearing potential not using reliable and adequate contraceptive methods (defined as: use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; practicing abstinence; sterile) during the study, or sexually active male patients with partners of childbearing potential unwilling to practice effective contraception during the study.

Current participation in other clinical therapeutic studies.

Incapability of compliance to the treatment protocol, in the opinion of the Investigator.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01473810